IN THIS ISSUE

FACULTY NEWS

The Department of Biological Sciences would like to formally welcome Dr. Lisa Petrella to our faculty. Dr. Petrella comes to us from the University of California at Santa Cruz, where she completed her Postdoctoral Fellowship in Dr. Susan Strome's laboratory. Dr. Petrella's research examines chromatin and gene expression responses to temperature in C. elegans. This semester, she is teaching our General Biology course.

Congratulations are in order for Dr. James Maki, who was promoted last spring to Full Professor. Dr. Maki has been a faculty member of the MU Department of Biological Sciences since 1992, and the research in his laboratory continues to involve oral, freshwater and marine microbiology.

Dr. Allison Abbott was invited to be a featured speaker at The MicroRNA Revolution: The 2012 Dr. Paul Janssen Award Symposium this September in New York City. This symposium honored Drs. Victor Ambros and Gary Ruvkun who identified and characterized the first microRNA. Dr. Ambros'
laboratory yielded the discovery of the first microRNA and Dr. Ruvkun's
laboratory identified how that microRNA regulates its target messenger.
Together, they demonstrated that the microRNA inactivates its target
through direct, base-pairing interactions. Since their discovery, the
small RNA field has grown to thousands of papers, many focused on
particular diseases and potential treatments. Dr. Abbott, who worked in Dr. Ambros' lab as a post-doctoral fellow, discussed genetic approaches used to identify pathways and targets regulated by micro RNAs in animal development.

GRANTS

Three of our faculty have recently been awarded grants to further their research

Dr. Rosemary Stuart was recently awarded two grants, one from NSF and the other from NIH. The NIH funded grant (which began Sept.. 1st 2012) is an AREA (R15) grant to study and characterize a novel subunit of the mitochondrial cytochrome c oxidase complex which we recently identified. This new subunit (termed Rcf1 in yeast) is a member of an evolutionarily conserved family of proteins termed the hypoxia induced gene 1 protein family (Hig1 proteins). The Stuart lab will be studying the function of the Hig1 proteins using both a yeast and a nematode (C. elegans) system. Their evidence is that the Hig1 proteins may serve to regulate the cytochrome c oxidase complex in response to changes in the metabolic requirements of the cells. The preliminary data used to support the grant application was from two previous undergraduate students in our lab (Andrew Furness and Micaela Robb-McGrath, now at Uterovesical/PhD and University of Maryland, Me School, respectively) and two current graduate students, Vera Stereologies and Joshua Garlics.

The NSF funded grant (also started Sept 1st, 2012) is to study the assembly and composition of the mitochondrial ribosome system. The translational activity of the mitochondrial ribosomes is critical for the biogenesis of the mitochondrial oxidative phosphorylation system, as key subunits of this system are encoded by the mitochondrial genome and thus are synthesized by the mitochondrial ribosomes. The Stuart lab proposes to further characterize a novel yeast mutant that they isolated, which is defective in the assembly of the mitochondrial ribosomes. They propose to use this mutant to map the assembly pathway of the ribosomes and to identify and characterize different functional regions of the ribosome. The preliminary data used to support the grant application was from two previous graduate students in Dr. Stuart’s lab, Drs. Lixia Jia and Jasvinder Kaur, who are currently performing post-docs at Washington University, St. Louis and University of California- San Francisco, respectively.

Dr. Martin St. Maurice has received a 3 year grant from NIH to study and biochemically characterize a fungal enzyme that may be a key therapeutic target in protecting immunocompromised patients from systemic yeast infections. Candida albicans is a ubiquitous yeast with which all of us are in regular contact. It is responsible for superficial and easily treated infections such as oral thrush or vaginitis. However, Candida infections can occasionally spread through the body and become life threatening. This is a particular concern for patients with weakened immune systems, such as late stage AIDS patients, patients undergoing chemotherapy, and organ transplant recipients. Dr. St. Maurice’s lab is researching an enzyme called urea amidolyase that is unique to just a few fungal species, including Candida. Research from other groups has shown that this enzyme is required for Candida to escape basic immune defenses and spread through the host. By better characterizing the structure and function of this enzyme, they hope to contribute to the development of therapeutic agents that will help immunocompromised patients fight systemic Candida infections.

Urea amidolyase is a complex enzyme, with many components and moving parts. The St. Maurice lab’s approach is to characterize the structure of the individual components by X-ray crystallography and, ultimately, to determine the structure of the entire enzyme. They have determined the first structure of this enzyme’s amidase domain, revealing many new insights into how this component of the enzyme functions. Their next challenge is to begin connecting the structures of the enzyme’s individual components into a more complete picture of how the enzyme functions as a whole. The lab uses X-ray crystallography, enzyme kinetics, and yeast genetics to better characterize this complicated and important human health target.

The expression of defective RNAs can have pathological effects through ectopic or failed expression of proteins. Dr. James Anderson’s lab addresses fundamental questions about a mechanism required for the degradation of improperly formed RNAs. Nuclear RNA quality control and many normal RNA processing events in the eukaryotic nucleus critically depend on TRAMP complexes (an assembly of a non-canonical poly(A) polymerase, a Zn-knuckle protein, and a RNA helicase). There is an emerging picture suggesting that functions of the TRAMP complex, such as RNA recognition, adenylation and unwinding, are coordinated to ensure correct outcomes of processing and/or degradation of a wide variety of substrates. However, relatively little is understood regarding how the individual components of TRAMP interact to facilitate such coordination. Moreover, despite the key role of TRAMP in eukaryotic RNA metabolism, it remains unclear how TRAMP manages the remarkable feat of identifying and processing a specific, yet vastly diverse set of RNAs that are synthesized by different RNA polymerases, have no obvious common sequence or secondary structure, and share no common associated proteins. The goal of Dr. Anderson’s recently awarded NIH grant is to understand how TRAMP mediated degradation or processing of cellular RNAs impacts cellular health. To do this, they will use genetic screens to determine the function of a specific region of the RNA helicase portion of TRAMP complexes, develop methods to assay TRAMP substrate polyadenlation and structure within live yeast cells to work towards identifying features that make particular RNAs preferred substrates for the TRAMP complex, and explore potential roles of a Zn-knuckle protein in RNA binding and protein-protein interaction.

Dr. Anderson designed the study to provide extensive opportunities for both graduate student and undergraduate student participation. The common yeast, S. cerevisiae, has many well-known characteristics that make it a strong system for teaching and research, including its ease of culture and manipulation, short life cycle, ease of performing genetic analysis, and completely sequenced genome. Already, three undergraduate students, Justin Heilberger, Alexis Onderak and Joseph Burclaff had contributed to the project through their independent study projects. Yan Li is a graduate student in Dr. Anderson’s Lab, and has generated the preliminary data for screening of Mtr4p arch domain mutants. This work will be continued as her dissertation. Dr. Jane Dorweiler oversees the daily functions of the lab, and will be carrying out experiments to express, purify and characterize Air proteins, as well as purifying wild-type and hypomodified tRNAiMet from yeast for use in the in vitro studies.